Monoclinic human insulin in complex with p-coumaric acid

Hormone secreted by pancreatic islet beta cells, that is the principal anabolic regulator of glucose, lipid, and protein metabolism and the central controller of blood glucose homeostasis ^[1]. Acts by binding to and activating the insulin receptor INSR, a receptor tyrosine kinase, triggering INSR autophosphorylation and recruitment/phosphorylation of insulin receptor substrate proteins IRS1 and IRS2, which activate the downstream PI3K/AKT and RAS/MAPK signaling cascades ^[2]. Through the PI3K/AKT pathway, stimulates glucose uptake into skeletal muscle and adipose tissue by promoting translocation of the glucose transporter GLUT4/SLC2A4 from intracellular storage vesicles to the plasma membrane ^[3].

In liver and muscle, promotes glycogen synthesis through AKT-mediated inhibitory phosphorylation of glycogen synthase kinase-3 (GSK3), thereby activating glycogen synthase ^[4]. In the liver, suppresses hepatic glucose production by inhibiting gluconeogenesis, in part through phosphorylation and exclusion of the FOXO1 transcription factor, which downregulates the gluconeogenic enzymes PEPCK and glucose-6-phosphatase ^[5]. In adipose tissue, promotes lipogenesis and potently suppresses lipolysis, reducing the flux of free fatty acids and glycerol to the liver and thereby further restraining hepatic gluconeogenesis ^[6]